Carcinoid crisis: The challenge is still there.

Carcinoid crisis (CC) has classically been considered the extreme end of the spectrum of carcinoid syndrome (CS). However, this presumption and other aspects of CC remain poorly understood. Consequently, current clinical guidelines are based on a low quality of evidence. There is no standard definition of CC and its incidence is unknown. Patients with florid CS and elevated serotonin (or its derivatives) which develop CC have been reported during decades. Nevertheless, the hypothesis that CC is due to the sudden massive release of serotonin or other vasoactive substances is unproven. Many triggers of CC (surgery, anaesthesia, peptide receptor radionuclide therapy, tumour biopsy or liver-directed treatments) have been proposed. However, data from studies are heterogeneous and even contradictory. Finally, the role of octreotide in the prevention of CC has been questioned. Herein, we report a clinical case and perform a critical review of the evidence available today on this topic.

Transitions in chromatin conformation shaped by fatty acids and the circadian clock underlie hepatic transcriptional reorganization in obese mice.

The circadian clock system coordinates metabolic, physiological, and behavioral functions across a 24-h cycle, crucial for adapting to environmental changes. Disruptions in circadian rhythms contribute to major metabolic pathologies like obesity and Type 2 diabetes. Understanding the regulatory mechanisms governing circadian control is vital for identifying therapeutic targets. It is well characterized that chromatin remodeling and 3D structure at genome regulatory elements contributes to circadian transcriptional cycles; yet the impact of rhythmic chromatin topology in metabolic disease is largely unexplored. In this study, we explore how the spatial configuration of the genome adapts to diet, rewiring circadian transcription and contributing to dysfunctional metabolism. We describe daily fluctuations in chromatin contacts between distal regulatory elements of metabolic control genes in livers from lean and obese mice and identify specific lipid-responsive regions recruiting the clock molecular machinery. Interestingly, under high-fat feeding, a distinct interactome for the clock-controlled gene Dbp strategically promotes the expression of distal metabolic genes including Fgf21. Alongside, new chromatin loops between regulatory elements from genes involved in lipid metabolism control contribute to their transcriptional activation. These enhancers are responsive to lipids through CEBPß, counteracting the circadian repressor REVERBa. Our findings highlight the intricate coupling of circadian gene expression to a dynamic nuclear environment under high-fat feeding, supporting a temporally regulated program of gene expression and transcriptional adaptation to diet.

Natural history and surgical outcomes of Rathke's cleft cysts: a Spanish multicenter study.

Rathke's cleft cysts (RCC) are a common type of lesion found in the sellar or suprasellar area. They are usually monitored clinically, but in some cases, surgery may be required. However, their natural progression is not yet well understood, and the outcomes of surgery are uncertain. The objective of this study is to evaluate the natural history of Rathke's cleft cysts in patients who are clinically monitored without treatment, and to determine the outcomes of surgery and the incidence of recurrences over time. Design and patients: National multicentric study of patients diagnosed of Rathke's cleft cyst (RCC- Spain) from 2000 onwards and followed in 15 tertiary centers of Spain. A total of 177 patients diagnosed of RCC followed for 67.3 months (6-215) and 88 patients who underwent surgery, (81 patients underwent immediate surgery after diagnosis and 7 later for subsequent growth) followed for 68.8 months (3-235). Results: The cyst size remained stable or decreased in 73.5% (133) of the patients. Only 44 patients (24.3%) experienced a cyst increase and 9 of them (5.1%) experienced an increase greater than 3 mm. In most of the patients who underwent surgery headaches and visual alterations improved, recurrence was observed in 8 (9.1%) after a median time of 96 months, and no predictors of recurrence were discovered. Conclusions: Rathke's cleft cysts without initial compressive symptoms have a low probability of growth, so conservative management is recommended. Patients who undergo transsphenoidal surgery experience rapid clinical improvement, and recurrences are infrequent. However, they can occur after a long period of time, although no predictors of recurrence have been identified.

Intracranial hypertension secondary to unruptured pial arteriovenous malformation. Suitability of isolated endovascular treatment with ethylene vinyl alcohol/dimethyl sulfoxide (Onyx®). Case report and literature review.

A 36-year-old male presented to the Emergency Department with clinical symptoms of blurred vision of progressive onset of two years of evolution. The ophthalmological examination revealed the existence of bilateral papilledema. Using cranial computed tomography and magnetic resonance imaging, the presence of a right occipital pial arteriovenous malformation was certified. Arteriographically, pial arterial contributions dependent on the right middle cerebral artery and the right posterior cerebral artery were identified. Venous drainage was located at the level of the superior sagittal sinus. An associated right transverse sinus stenosis was also identified. The existence of secondary intracranial hypertension was corroborated by monitoring with an intracranial pressure sensor. An interventional procedure was carried out consisting of embolization of the arterial supplies of the lesion using Onyx®. The clinical-radiological findings after the procedure were favorable: the papilledema disappeared and complete exclusion of the malformation was achieved. A new intracranial pressure measurement showed resolution of intracranial hypertension. Subsequent regulated radiological controls showed complete exclusion of the malformation up to 5 years later.

WRN inhibition leads to its chromatin-associated degradation via the PIAS4-RNF4-p97/VCP axis.

Synthetic lethality provides an attractive strategy for developing targeted cancer therapies. For example, cancer cells with high levels of microsatellite instability (MSI-H) are dependent on the Werner (WRN) helicase for survival. However, the mechanisms that regulate WRN spatiotemporal dynamics remain poorly understood. Here, we used single-molecule tracking (SMT) in combination with a WRN inhibitor to examine WRN dynamics within the nuclei of living cancer cells. WRN inhibition traps the helicase on chromatin, requiring p97/VCP for extraction and proteasomal degradation in a MSI-H dependent manner. Using a phenotypic screen, we identify the PIAS4-RNF4 axis as the pathway responsible for WRN degradation. Finally, we show that co-inhibition of WRN and SUMOylation has an additive toxic effect in MSI-H cells and confirm the in vivo activity of WRN inhibition using an MSI-H mouse xenograft model. This work elucidates a regulatory mechanism for WRN that may facilitate identification of new therapeutic modalities, and highlights the use of SMT as a tool for drug discovery and mechanism-of-action studies.

Effects of a web application based on multimedia animations to support therapeutic exercise for rotator cuff-related shoulder pain: protocol for an open-label randomised controlled trial.

INTRODUCTION: Rotator cuff-related shoulder pain (RCRSP) is the most common cause of shoulder pain. Currently, exercise is proposed as the first-line treatment for patients suffering from RCRSP. However, adherence to therapeutic exercise programmes can be poor in the long term in a home setting. The aim of this study is to evaluate the effects of adding video animations to a traditional paper-based exercise programme. METHODS AND ANALYSIS: A single-centre, randomised, open-labelled clinical trial will be conducted in a hospital in Spain. Adults aged between 18 and 80 years diagnosed with RCRSP who meet the eligibility criteria will be included. Patients (n=132) will be randomised into two groups, with both receiving paper-based exercises, and the experimental group will also be provided with video animations. The participants will receive seven face-to-face physical therapy sessions and will be asked to perform the exercises at home for 6 months. The primary outcome measure will be the Shoulder Pain and Disability Index, measured at baseline, 3 weeks, 3 months (primary analysis) and 6 months. Secondary outcomes will be the patient's pain intensity during the last week (rest, during movement and at night); expectations of improvement; satisfaction with treatment; impression of improvement; perceived usability, usefulness and satisfaction of multimedia animations; and adherence to exercises. Generalised least squares regression models with an autoregressive-moving average lag one correlation structure will be implemented, with an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee of Hospital Universitario Fundación Alcorcón (Madrid, Spain), reference number CI18/16. All participants will sign an informed consent. The results will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05770908.

Giant solitary fibrous tumor of the olfactory groove. An unusual simulator in an unusual location.

Solitary fibrous tumors are rare mesenchymal neoplasms that can develop in any part of the body, with those that settle intracranially being confused with meningiomas as a general rule. We present the case of a 57-year-old man referred to our hospital due to bifrontal headache, anosmia, and behavioral alterations of 6 months' duration. Radiological studies revealed the existence of a large tumor mass with an extra-axial appearance and location in the anterior cranial fossa, initially compatible with a giant meningioma of the olfactory groove. Gross total resection of the mass was carried out. The pathological diagnosis was unexpected: a solitary fibrous tumor (WHO grade 1, 2021). Given the aggressive nature of these lesions, with a tendency to recurrence, malignant transformation and even metastasis, surgery with macroscopically complete resection intention should constitute the first therapeutic option. Close clinical-radiological follow-up after the procedure is justified.

[Thyroid surgery in a context of scarce resources at Saint Martin de Porres Dominican Hospital (Yaounde, Cameroon)]. / Chirurgie thyroïdienne dans le contexte de populations avec de faibles ressources à l'hôpital dominicain Saint Martin de Porres (Yaoundé, Cameroun).

Introduction: Surgical campaigns for thyroid surgery in low-income environments are very efficient, but there is little literature reporting results. These campaigns are complex due to multiple particularities: highly evolved cases, the need for professionals to travel or an obvious socio-cultural barrier influence towards the surgical act. We describe a surgical campaign in Cameroon to treat patients with goiter and issue some medical and sociocultural recommendations in view of our experience for its implementation with guarantees. Material and methods: An experienced group carried out an 11-day campaign at the Saint Martin de Porres Dominican Hospital, Yaounde, Cameroon. Demographic data, TSH values, surgery and complications after a 12-month follow-up were analyzed. Results: Thirty-eight patients with goiter were selected for the campaign and 32 patients (mean age, 40-years-old; 30 females) were operated. Bilateral goiter, as assessed with echography, was diagnosed in 13 patients (41%). Ten patients (31%) had a WHO grade II goiter (visible with the neck in a normal position). The surgical procedures were 18 unilateral thyroidectomy with isthmectomie, 13 total thyroidectomy, and 1 totalizing thyroidectomy, due to previous unilateral thyroidectomy (cancer recurrence). A pathological study in 13 patients (40%, extra cost 60 €) showed benign multinodular goiter/thyroid nodule (12 patients) and an extensive papillary carcinoma (one patient). Six months postoperatively, 3 patients had a slight dysphonia and one patient had persistent hypocalcemia. Follow-up was completed in all patients, either face to face (75%, 24 patients) or by phone (25%, 8 patients who failed to have a TSH test because of its cost, 23 €). Conclusions: Surgical campaigns to treat thyroid pathology can be carried out with guarantees if a series of important steps are followed: active participation of the patient's environment, thyroid ultrasound by the surgical team to decide which technique, intense awareness about monitoring and hormone replacement therapy, and the participation of local personnel for long-term follow-up.

Glucose metabolism outcomes after pituitary surgery in patients with acromegaly.

AIM: To investigate the impact of pituitary surgery on glucose metabolism and to identify predictors of remission of diabetes after pituitary surgery in patients with acromegaly. METHODS: A national multicenter retrospective study of patients with acromegaly undergoing transsphenoidal surgery for the first time at 33 tertiary Spanish hospitals (ACRO-SPAIN study) was performed. Surgical remission of acromegaly was evaluated according to the 2000 and 2010 criteria. RESULTS: A total of 604 acromegaly patients were included in the study with a total median follow up of 91 months (interquartile range [IQR] 45-163). At the acromegaly diagnosis, 23.8% of the patients had diabetes mellitus (DM) with a median glycated hemoglobin (HbA1c) of 6.9% (IQR 6.4-7.9) [51.9 mmol/mol (IQR 46.4-62.8)]. In the multivariate analysis, older age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), dyslipidemia (OR 5.25, 95% CI 2.81 to 9.79), arthropathy (OR 1.39, 95% CI 2.82 to 9.79), and higher IGF-I levels (OR 1.30, 95% CI 1.05 to 1.60) were associated with a greater prevalence of DM. At the last follow-up visit after surgery, 21.1% of the DM patients (56.7% of them with surgical remission of acromegaly) experienced diabetes remission. The cure rate of DM was more common in older patients (hazard ratio [HR] 1.77, 95% CI 1.31 to 2.43), when surgical cure was achieved (HR 2.10, 95% CI 1.01 to 4.37) and when anterior pituitary function was not affected after surgery (HR 3.38, 95% CI 1.17 to 9.75). CONCLUSION: Glucose metabolism improved in patients with acromegaly after surgery and 21% of the diabetic patients experienced diabetes remission; being more frequent in patients of older age, and those who experienced surgical cure and those with preserved anterior pituitary function after surgery.

Effectiveness of combined first-line medical treatment in acromegaly with prolactin cosecretion.

OBJECTIVE: The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin cosecreting PA (GH&PRL-PA). DESIGN: This is a retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least 6 months of first-line medical treatment. METHODS: Baseline characteristics, first-line medical treatment strategies, and outcomes were analyzed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality. RESULTS: Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs 51.9 ± 12.7 years, P < .01) and harboring more frequently macroadenomas (89.7% vs 72.1%, P = .03). First-generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs 15.2%, P < .01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs 55.1%, P = .04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline. CONCLUSION: In GH&PRL-PA, the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first-line medical treatment in combination with fgSRLs in these subgroups of patients.

Pegvisomant and pasireotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition.

During neural tube (NT) development, the notochord induces an organizer, the floorplate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors. Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously form floorplates without the notochord, demonstrating that stem cells can self-organize without embryonic inducers. Here, we investigated floorplate self-organization in clonal mouse NTOs. Expression of the floorplate marker FOXA2 was initially spatially scattered before resolving into multiple clusters, which underwent competition and sorting, resulting in a stable "winning" floorplate. We identified that BMP signaling governed long-range cluster competition. FOXA2+ clusters expressed BMP4, suppressing FOXA2 in receiving cells while simultaneously expressing the BMP-inhibitor NOGGIN, promoting cluster persistence. Noggin mutation perturbed floorplate formation in NTOs and in the NT in vivo at mid/hindbrain regions, demonstrating how the floorplate can form autonomously without the notochord. Identifying the pathways governing organizer self-organization is critical for harnessing the developmental plasticity of stem cells in tissue engineering.

Impact of suppression of the SOS response on protein expression in clinical isolates of Escherichia coli under antimicrobial pressure of ciprofloxacin.

Introduction/objective: Suppression of the SOS response in combination with drugs damaging DNA has been proposed as a potential target to tackle antimicrobial resistance. The SOS response is the pathway used to repair bacterial DNA damage induced by antimicrobials such as quinolones. The extent of lexA-regulated protein expression and other associated systems under pressure of agents that damage bacterial DNA in clinical isolates remains unclear. The aim of this study was to assess the impact of this strategy consisting on suppression of the SOS response in combination with quinolones on the proteome profile of Escherichia coli clinical strains. Materials and methods: Five clinical isolates of E. coli carrying different chromosomally- and/or plasmid-mediated quinolone resistance mechanisms with different phenotypes were selected, with E. coli ATCC 25922 as control strain. In addition, from each clinical isolate and control, a second strain was created, in which the SOS response was suppressed by deletion of the recA gene. Bacterial inocula from all 12 strains were then exposed to 1xMIC ciprofloxacin treatment (relative to the wild-type phenotype for each isogenic pair) for 1 h. Cell pellets were collected, and proteins were digested into peptides using trypsin. Protein identification and label-free quantification were done by liquid chromatography-mass spectrometry (LC-MS) in order to identify proteins that were differentially expressed upon deletion of recA in each strain. Data analysis and statistical analysis were performed using the MaxQuant and Perseus software. Results: The proteins with the lowest expression levels were: RecA (as control), AphA, CysP, DinG, DinI, GarL, PriS, PsuG, PsuK, RpsQ, UgpB and YebG; those with the highest expression levels were: Hpf, IbpB, TufB and RpmH. Most of these expression alterations were strain-dependent and involved DNA repair processes and nucleotide, protein and carbohydrate metabolism, and transport. In isolates with suppressed SOS response, the number of underexpressed proteins was higher than overexpressed proteins. Conclusion: High genomic and proteomic variability was observed among clinical isolates and was not associated with a specific resistant phenotype. This study provides an interesting approach to identify new potential targets to combat antimicrobial resistance.

Neuroendoscopic access to the third ventricle in patients with narrow foramen of monro without stenosis/obstruction: role of foraminoplasty.

OBJECT: One of the critical steps for the success of intraventricular neuroendoscopic procedures is the entry into the third ventricle and passage of the endoscopy system through the foramen of Monro (FM). A diameter larger than that of the instrument used is considered a prerequisite for safely performing the technique, as damage to this structure can lead to alterations in the fornix and vascular structures. When the foramen diameter is narrow and there is no obstruction/stenosis, the role of foraminoplasty in reducing the risk of complications has not been adequately assessed in the literature. METHODS: A review of endoscopic procedures conducted at our center since 2018 was undertaken. Cases in which preoperative imaging indicated a FM diameter < 6 mm and foraminoplasty technique was applied were examined to determine the technical and functional success of the procedure. The technical success was determined by completing the neuroendoscopic procedure with the absence of macroscopic lesions in the various structures comprising the foramen and without complications in the follow-up imaging tests. Functional success was defined as the absence of cognitive/memory alterations during the 3-month postoperative follow-up. Additionally, a review of the various forms of foraminoplasty described in the literature is conducted. RESULTS: In our cohort, six patients were identified with a preoperative FM diameter < 6 mm without obstruction or stenosis. Foraminoplasty was planned for these cases to facilitate various intraventricular neuroendoscopic procedures. In all instances, the technique was successfully performed without causing macroscopic damage to the structures comprising the foramen. Follow-up visits included various cognitive tests to assess potential sequelae related to microscopic damage to the fornix. None of the patients exhibited anomalies. CONCLUSION: Foraminoplasty in patients with a narrow FM without signs of stenosis/obstruction is a useful technique to reduce the risk of complications during the passage of the endoscopy system through this structure, enabling the safe performance of neuroendoscopic procedures.

Dynamic Workflow Proposal for Continuous Frameless Electromagnetic Neuronavigation in Rigid Neuroendoscopy.

BACKGROUND: Ventriculoscopic neuronavigation has been described in several articles. However, there are different ventriculoscopes and navigation systems. Due to these different combinations, it is difficult to find detailed neuronavigation protocols. We describe, step-by-step, a simple method to navigate both the trajectory until reaching the ventricular system, as well as the intraventricular work. METHODS: We use a rigid ventriculoscope (LOTTA, KarlStorz) with an electromagnetic stylet (S8-StealthSystem, Medtronic). The protocol is based on a modified or 3-dimensionally printed trocar for navigating the extraventricular step and on a modified pediatric nasogastric tube for the intraventricular navigation. RESULTS: This protocol can be set up in less than 10 minutes. The extraventricular part is navigated by introducing the electromagnetic stylet inside the modified or 3-dimensionally printed trocar. Intraventricular navigation is done by combining a modified pediatric nasogastric tube with the electromagnetic stylet inside the endoscope's working channel. The most critical point is to obtain a blunt-bloodless ventriculostomy while achieving perfect alignment of all targeted structures via pure straight trajectories. CONCLUSIONS: This protocol is easy-to-set-up, avoids head rigid-fixation and bulky optical-based attachments to the ventriculoscope, and allows continuous navigation of both parts of the surgery. Since we have implemented this protocol, we have noticed a significant enhancement in both simple and complex ventriculoscopic procedures because the surgery is dramatically simplified.

Heterogeneity of SOS response expression in clinical isolates of Escherichia coli influences adaptation to antimicrobial stress.

In recent years, new evidence has shown that the SOS response plays an important role in the response to antimicrobials, with involvement in the generation of clinical resistance. Here we evaluate the impact of heterogeneous expression of the SOS response in clinical isolates of Escherichia coli on response to the fluoroquinolone, ciprofloxacin. In silico analysis of whole genome sequencing data showed remarkable sequence conservation of the SOS response regulators, RecA and LexA. Despite the genetic homogeneity, our results revealed a marked differential heterogeneity in SOS response activation, both at population and single-cell level, among clinical isolates of E. coli in the presence of subinhibitory concentrations of ciprofloxacin. Four main stages of SOS response activation were identified and correlated with cell filamentation. Interestingly, there was a correlation between clinical isolates with higher expression of the SOS response and further progression to resistance. This heterogeneity in response to DNA damage repair (mediated by the SOS response) and induced by antimicrobial agents could be a new factor with implications for bacterial evolution and survival contributing to the generation of antimicrobial resistance.

First Report of the Emerging Pathogen Kodamaea ohmeri in Honduras.

Kodamaea ohmeri is an environmental yeast considered a rare emerging pathogen. In clinical settings, the correct identification of this yeast is relevant because some isolates are associated with resistance to antifungals. There is a lack of available data regarding the geographical distribution, virulence, and drug resistance profile of K. ohmeri. To contribute to the knowledge of this yeast, this study aimed to describe in depth three isolates of K. ohmeri associated with fungemia in Honduras. The identification of the isolates was carried out by sequencing the ribosomal ITS region. In addition, the susceptibility profile to antifungals was determined, and some properties associated with virulence were evaluated (exoenzyme production, biofilm formation, cell adhesion, and invasion). The isolates showed strong protease, phospholipase, and hemolysin activity, in addition to being biofilm producers. Adherence and invasion capacity were evident in the HeLa and Raw 264.7 cell lines, respectively. This study expands the understanding of the underlying biological traits associated with virulence in K. ohmeri, and it is the first report of the detection and identification of K. ohmeri in Honduras as a cause of human infection.